AstraZeneca and Amgen Submit BLA for Tezepelumab, a First-in-Class Anti-TSLP Monoclonal Antibody for Severe Asthma

May 12, 2021 News /BioValleyBIOON/ -- Amgen recently announced that its partnerAstraZeneca(AstraZeneca) has submitted to the U.S. Food and Drug Administration (FDA) submitted a Biologics License Application (BLA) for the antibody drug tezepelumab for the treatment of severe asthma.Tezepelumab is the first in a wide range of severeAsthmaBiologics that can continuously and significantly reduce disease progression in the patient population. In 2018, the United StatesFDATezepelumab was granted Breakthrough Therapy Designation (BTD).

Tezepelumab is a potential first-in-class drug that blocks the action of thymic stromal lymphopoietin (TSLP), an epithelial cytokine, inAsthmaPlays a key role in inflammation.

The BLA for this drug is based on positive data from the PATHFINDER clinical program, including positive results from the pivotal Phase 3 NAVIGATOR trial. The trial demonstrated that, in a broad population of patients with severe uncontrolled asthma, compared with placebo,tezepelumab makesAsthmaAnnualized Exacerbation Rate (AAER) showed a statistically significant and clinically meaningful reduction。It is worth noting that tezepelumab is the only agent capable of consistently and significantly reducing broad severeAsthmaBiologics for Patient AAER, Regardless of Phase 2 and Phase 3Clinical TrialWhat was the baseline eosinophil count in patients?

David M. Reese, M.D., Executive Vice President of Research and Development at Amgen, stated, “Although therapies are currently available for this complex and often debilitating disease, severe asthma remains uncontrolled for many patients. This application brings us closer to providing a broad range of severeAsthmaproviding a potentially transformative treatment option for patient populations, including those with different phenotypes and differentBiomarkerspatient population.”

The NAVIGATOR trial was the first Phase III study to demonstrate therapeutic benefits of targeting TSLP in severe asthma. The trial results were announced in November 2020, showing that the study met its primary endpoint: in the overall patient population, treatment with tezepelumab plus standard of care (SoC) reduced annualized asthma exacerbation rates over 52 weeks compared with placebo plus SoC.AsthmaA statistically significant and clinically meaningful reduction in the annualized exacerbation rate (AAER). In this trial, standard of care (SoC) consisted of medium- or high-dose inhaled corticosteroids (ICS) plus one additional controller medication, with or without oral corticosteroids (OCS).

Furthermore, in the subgroup of patients with baseline eosinophil counts <300 cells/μL, the trial also met its primary endpoint: treatment with tezepelumab + SoC resulted in a statistically significant and clinically meaningful reduction in AAER compared with placebo + SoC. A similar reduction in AAER was observed in the subgroup of patients with baseline eosinophil counts <150 cells/μL.

In terms of safety, tezepelumab in severeAsthmaPatients demonstrated good tolerability. Preliminary analyses showed no clinically meaningful differences in safety outcomes between the tezepelumab treatment group and the placebo group.

Detailed data from this trial will be presented at the American Thoracic Society (ATS) 2021 International Conference, to be held in late May 2021.Conferencepublished above.

Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine produced in response to pro-inflammatory stimuli, such as pulmonary allergens, viruses, and other pathogens, playing a pivotal role in the initiation and persistence of airway inflammation. TSLP drives the release of downstream type 2 (T2) cytokines, including interleukin-4 (IL-4), IL-5, and IL-13, leading to inflammation and asthma symptoms. TSLP can also activate various cell types involved in non-T2-driven inflammation. Consequently, the early upstream activity of TSLP in the inflammatory cascade has been identified as a potential therapeutic target in a broad population of patients with asthma. Blocking TSLP can prevent immune cells from releasing pro-inflammatory cytokines, thereby preventing asthma exacerbations and improvingAsthmaControl.

Tezepelumab is a first-in-class anti-TSLP monoclonal antibody drug that specifically binds to human TSLP and blocks its interaction with the receptor complex, thereby preventing the release of pro-inflammatory cytokines by TSLP-targeted immune cells, thus preventing asthma attacks and improving asthma control. Due to its action on the early upstream of the inflammatory cascade, tezepelumab may be suitable for a wide range of severe uncontrolledAsthmaPatients, regardless of patient phenotype or T2BiomarkersStatus.

Currently, tezepelumab is being jointly developed by AstraZeneca and Amgen. The industry believes that if tezepelumab successfully launches on the market, it willAsthmaThe therapeutic field is undergoing a dramatic upheaval, with its target patient population far exceeding that of currently marketed biologics, includingGlaxoSmithKline(GSK)’s Nucala (mepolizumab, targeting IL-5), Teva’s Cinqair (reslizumab, targeting IL-5), and biologic therapies currently under development for the treatment of asthma, such as AstraZeneca’s benralizumab (targeting the IL-5 receptor alpha subunit [IL-5Rα]) and Sanofi’s Dupixent (targeting IL-4/IL-13). All four of these therapies target only specific inflammatory molecules that drive asthma inflammation and are suitable only for certain types of patients with severe asthma, namely, specific patient subgroups, such as those with eosinophilic asthma.Asthma. (Bioon.com)

Original Source: Amgen Announces Tezepelumab Biologics Licenseapplication Submitted To U.S. FDA